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Modeling the Breakage-Fusion-Bridge Mechanism: Combinatorics and Cancer Genomics

  • Marcus Kinsella
  • Vineet Bafna
Part of the Lecture Notes in Computer Science book series (LNCS, volume 7262)

Abstract

The breakage-fusion-bridge (BFB) mechanism was proposed over seven decades ago and is a source of genomic variability and gene amplification in cancer. Here we formally model and analyze the BFB mechanism, to our knowledge this first time this has been undertaken. We show that BFB can be modeled as successive inverted prefix duplications of a string. Using this model, we show that BFB can achieve a surprisingly broad range of amplification patterns. We find that a sequence of BFB operations can be found that nearly fits most patterns of copy number increases along a chromosome. We conclude that this limits the usefulness of methods like array CGH for detecting BFB and discuss other implications for understanding mechanisms of genomic instability.

Keywords

cancer genomics algorithms combinatorial pattern matching gene amplification 

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References

  1. 1.
    Artandi, S.E., DePinho, R.A.: Telomeres and telomerase in cancer. Carcinogenesis 31, 9–18 (2010)CrossRefGoogle Scholar
  2. 2.
    Bignell, G.R., Santarius, T., Pole, J.C., Butler, A.P., Perry, J., Pleasance, E., Greenman, C., Menzies, A., Taylor, S., Edkins, S., Campbell, P., Quail, M., Plumb, B., Matthews, L., McLay, K., Edwards, P.A., Rogers, J., Wooster, R., Futreal, P.A., Stratton, M.R.: Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution. Genome Res. 17, 1296–1303 (2007)CrossRefGoogle Scholar
  3. 3.
    Deza, M.M., Deza, E.: Encyclopedia of Distances. Springer (2009)Google Scholar
  4. 4.
    Kitada, K., Yamasaki, T.: The complicated copy number alterations in chromosome 7 of a lung cancer cell line is explained by a model based on repeated breakage-fusion-bridge cycles. Cancer Genet. Cytogenet. 185, 11–19 (2008)CrossRefGoogle Scholar
  5. 5.
    McClintock, B.: The Production of Homozygous Deficient Tissues with Mutant Characteristics by Means of the Aberrant Mitotic Behavior of Ring-Shaped Chromosomes. Genetics 23, 315–376 (1938)Google Scholar
  6. 6.
    McClintock, B.: The Stability of Broken Ends of Chromosomes in Zea Mays. Genetics 26, 234–282 (1941)Google Scholar
  7. 7.
    Santarius, T., Shipley, J., Brewer, D., Stratton, M.R., Cooper, C.S.: A census of amplified and overexpressed human cancer genes. Nat. Rev. Cancer 10, 59–64 (2010)CrossRefGoogle Scholar
  8. 8.
    Shimizu, N., Shingaki, K., Kaneko-Sasaguri, Y., Hashizume, T., Kanda, T.: When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation. Exp. Cell Res. 302, 233–243 (2005)CrossRefGoogle Scholar
  9. 9.
    Zhao, X., Li, C., Paez, J.G., Chin, K., Janne, P.A., Chen, T.H., Girard, L., Minna, J., Christiani, D., Leo, C., Gray, J.W., Sellers, W.R., Meyerson, M.: An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res. 64, 3060–3071 (2004)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Marcus Kinsella
    • 1
  • Vineet Bafna
    • 2
  1. 1.Bioinformatics and Systems Biology ProgramUniversity of CaliforniaSan DiegoUSA
  2. 2.Department of Computer Science and EngineeringUniversity of CaliforniaSan DiegoUSA

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